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Biomedical subjects

J Pena

Publications and source records attributed to J Pena.

At least 19 recordsLinked to original sources

Monte Carlo correction factors for a Farmer 0.6 cm3 ion chamber dose measurement in the build-up region of the 6 MV clinical beam.

Reference dosimetry of photon fields is a well-established subject and currently available protocols (such as the IAEA TRS-398 and AAPM TG-51) provide methods for converting the ionization chamber (IC) reading into dose to water, provided reference conditions of charged particle equilibrium (CPE) are fulfilled. But these protocols cannot deal with the build-up region, where the lack of CPE limits the applicability of the cavity theorems and so the chamber correction factors become depth dependent. By explicitly including the IC geometry in the Monte Carlo simulations, depth-dependent dose correction factors are calculated for a PTW 30001 0.6 cm(3) ion chamber in the build-up region of the 6 MV photon beam. The corrected percentage depth dose (PDD) agrees within 2% with that measured using the NACP 02 plane-parallel ion chamber in the build-up region at depths greater than 0.4 cm, where the Farmer chamber wall reaches the phantom surface.

Calibration↗

Monte Carlo study of Siemens PRIMUS photoneutron production.

Neutron production in radiotherapy facilities has been studied from the early days of modern linacs. Detailed studies are now possible using photoneutron capabilities of general-purpose Monte Carlo codes at energies of interest in medical physics. The present work studies the effects of modelling different accelerator head and room geometries on the neutron fluence and spectra predicted via Monte Carlo. The results from the simulation of a 15 MV Siemens PRIMUS linac show an 80% increase in the fluence scored at the isocentre when, besides modelling the components necessary for electron/photon simulations, other massive accelerator head components are included. Neutron fluence dependence on inner treatment room volume is analysed showing that thermal neutrons have a 'gaseous' behaviour and then a 1/V dependence. Neutron fluence maps for three energy ranges, fast (E > 0.1 MeV), epithermal (1 eV < E < 0.1 MeV) and thermal (E < 1 eV), are also presented and the influence of the head components on them is discussed.

Monte Carlo Method↗

Development and operation of a pixel segmented liquid-filled linear array for radiotherapy quality assurance.

A liquid isooctane (C(8)H(18)) filled ionization linear array for radiotherapy quality assurance has been designed, built and tested. The detector consists of 128 pixels, each of them with an area of 1.7 mm x 1.7 mm and a gap of 0.5 mm. The small pixel size makes the detector ideal for high gradient beam profiles such as those present in intensity modulated radiation therapy (IMRT) and radiosurgery. As the read-out electronics we use the X-ray Data Acquisition System with the Xchip developed by the CCLRC. Studies concerning the collection efficiency dependence on the polarization voltage and on the dose rate have been made in order to optimize the device operation. In the first tests, we have studied dose rate and energy dependences. Dose rate dependence was found to be lower than 2.1% up to 5 Gy min(-1), and energy dependence lower than 2.5% up to 20 cm depth in solid water. Output factors and penumbras for several rectangular fields have been measured with the linear array and were compared with the results obtained with a 0.125 cm(3) air ionization chamber and radiographic film, respectively. Finally, we have acquired profiles for an IMRT field and for a virtual wedge. These profiles have also been compared with radiographic film measurements. All the comparisons show a good correspondence. The device has proved its capability to verify on-line therapy beams with good spatial resolution and signal-to-noise ratio.

Dose-Response Relationship, Radiation↗

Commissioning of a medical accelerator photon beam Monte Carlo simulation using wide-field profiles.

A method for commissioning an EGSnrc Monte Carlo simulation of medical linac photon beams through wide-field lateral profiles at moderate depth in a water phantom is presented. Although depth-dose profiles are commonly used for nominal energy determination, our study shows that they are quite insensitive to energy changes below 0.3 MeV (0.6 MeV) for a 6 MV (15 MV) photon beam. Also, the depth-dose profile dependence on beam radius adds an additional uncertainty in their use for tuning nominal energy. Simulated 40 cm x 40 cm lateral profiles at 5 cm depth in a water phantom show greater sensitivity to both nominal energy and radius. Beam parameters could be determined by comparing only these curves with measured data.

Algorithms↗

Free ion yield observed in liquid isooctane irradiated by gamma rays. Comparison with the Onsager theory.

We have analysed data on the free ion yield observed in liquid isooctane irradiated by 60Co gamma rays within the framework of the Onsager theory about initial recombination. Several distribution functions describing the electron thermalization distance have been used and compared with the experimental results: a delta function, a Gaussian-type function and an exponential function. A linear dependence between the free ion yield and the external electric field has been found at low-electric-field values (E < or = 1.2 x 10(3) V mm(-1)) in excellent agreement with the Onsager theory. At higher electric field values, we obtain a solution in power series of the external field using the Onsager theory.

Cobalt Radioisotopes↗

Role of the carboxy-termini of tubulin on its chaperone-like activity.

Mutational analysis and the enzymatic digestion of many chaperones indicate the importance of both hydrophobic and hydrophilic residues for their unique property. Thus, the chaperone activity of alpha-crystallin is lost due to the substitution of hydrophobic residues or upon enzymatic digestion of the negatively charged residues. Tubulin, an eukaryotic cytoskeletal protein, exhibits chaperone-like activity as demonstrated by prevention of DTT-induced aggregation of insulin, thermal aggregation of alcohol dehydrogenase, betagamma-crystallin, and other proteins. We have shown that the tubulin lost its chaperone-like activity upon digestion of its negatively charged C-termini. In this article, the role of the C-terminus of individual subunits has been investigated. We observe that the digestion of C-terminus of beta-subunit with subtilisin causes loss of chaperone-like activity of tubulin. The contribution of C-terminus of alpha-subunit is difficult to establish directly as subtilisin cleaves C-terminus of beta-subunit first. This has been ascertained indirectly using a 14-residue peptide P2 having the sequence corresponding to a conserved region of MHC class I molecules and that binds tightly to the C-terminus of alpha-subunit. We have shown that the binding of P2 peptide to alphabeta-tubulin causes complete loss of its chaperone-like activity. NMR and gel-electrophoresis studies indicate that the P2 peptide has a significant higher binding affinity for the C-terminus of alpha-subunit compared to that of beta-subunit. Thus, we conclude that both the C-termini are necessary for the chaperone-like activity of tubulin. Implications for the chaperone functions in vivo have been discussed.

Amino Acid Sequence↗

Cellular localization of neuronal nitric oxide synthase (NOS-1) in the human and rat retina.

The neuronal form of nitric oxide synthase (NOS-1) has been localized to several cell types in the retinas of experimental animals; however, localization in the human retina has not been definitive. By using in situ hybridization and immunohistochemistry, we have compared the cellular expression and localization of NOS-1 in the rat and human retinas. In both rat and human retinas, NOS-1 is expressed in the inner segments of photoreceptors, cells in the inner nuclear layer, particularly amacrine cells, and retinal ganglion cells. In human cones, NOS-1 is abundantly present in the outer segments. In the rat, optic nerve transection caused a loss of cells that were positive for NOS-1 in the ganglion cell layer. Although a retinal ganglion cell localization has not been reported consistently in the literature, our data clearly localize NOS-1 to the retinal ganglion cells of the rat and human retinas.

Animals↗

Interstrain variation in the deoxynucleotide composition of Cryptococcus neoformans: nucleotide composition of Cryptococcus neoformans.

The deoxynucleotide (dNMP) composition of ten strains of C. neoformans was analysed by 32P-labelling and two-dimensional thin-layer chromatography. This technique is very sensitive for detecting rare deoxynucleotide adducts and analogues (minor bases) in DNA. The results indicate considerable variation among strains in DNA nucleotide composition.

Autoradiography↗

Anonymous testing of newborn infants for HIV antibodies as a basis for estimating prevalence of HIV in childbearing women: the 1991-1994 study in Spain.

During 1991-1994, anonymous screening of newborn infants for maternal antibody to human immunodeficiency virus (HIV) was carried out in three regions of Spain: Valencia, Galicia and Sevilla. The newborn infants whose heel-stick blood eluates were satisfactory for HIV antibody tests were a consecutive series of 104 876, representing 99.3% of all newborn infants undergoing routine metabolic screening and estimated as comprising at least 98% of all births in the three regions. Enzyme immunoassay (EIA) positives were confirmed by immunoblot, yielding 246 confirmations: a rate of 2.3 per 1000. Seropositivity rates ranged from 1.4 per 1000 in Galicia to 2.1 in Sevilla and 3.1 in Valencia, and remained relatively stable in each region during the years of the study. Within socioeconomically defined subgroups of birth hospitals in Valencia and Galicia, all subgroups contained seropositives, even though there was a twofold to fivefold over-representation in the "inner city" public hospitals. To estimate the proportion of HIV-1-seropositive newborn infants who were positive for HIV-1 DNA, polymerase chain reaction (PCR) assays were performed on 165 dried blood spots that had been retained following positive immunoblot assays. Fifteen (9%) were PCR positive, and when this proportion is adjusted for the age-specific sensitivity of the method, it translates into an estimated HIV-1 transmission rate of 24% (range 18-36%). For 94,906 of the 104,876 newborn infants screened, the EIA used could detect antibodies that react with epitopes of HIV-1 and HIV-2. There were 30 newborn infants whose blood eluate was positive by this combined HIV-1/HIV-2 antibody screen and whose secondary screening with monovalent HIV-2 and HIV-1 EIA indicated that the HIV-2 reactivity was above the cut-off whereas the HIV-1 was not. Ranking these 30 results according to absolute HIV-2 reactivity and relative reactivity with respect to HIV-1 indicated that four infants were probable true HIV-2 seropositives and a total of 12 were possible HIV-2 seropositives, a prevalence of the order of 1:10000 to 1:20000 newborn infants. These anonymous population-based serological studies provide "leading-indicator" data to complement traditional AIDS surveillance for epidemiological and planning purposes.

AIDS Serodiagnosis↗

Bcl-x rather than Bcl-2 mediates CD40-dependent centrocyte survival in the germinal center.

Both rapid B-cell proliferation and programmed cell death (PCD) occur during the differentiation and selection of B cells within the germinal center. To help elucidate the role of Bcl-x in B-cell antigen selection and PCD within the germinal center, we examined its expression in defined B-cell populations and by immunochemistry of tonsil tissue. Purified B-cell fractions enriched for centrocytes express high amounts of Bcl-x and relatively low amounts of Bcl-2, whereas fractions enriched for centroblasts lack significant levels of both proteins. Consistent with this observation, immunocytochemistry localized Bcl-x within cells scattered throughout the germinal center. Stimulation of tonsil B cells with either CD40 or Staphylococcus aureus Cowan increase bcl-x mRNA and protein levels. Treatment of a cell line with a germinal center phenotype (RAMOS) or the tonsillar B-cell centroblast fraction with CD40 rapidly increased Bcl-x levels and partially rescued B cells from PCD. These data suggest that Bcl-x rather than Bcl-2 may rescue centrocytes during selection in the germinal center.

Apoptosis↗

Glyburide increases the secretion, tissue uptake, and action of insulin in conscious normal dogs.

The action of glyburide on glucose homeostasis involves pancreatic and extrapancreatic mechanisms. The relative importance of each of these processes in the hypoglycemic response to sustained administration of glyburide is unknown. In addition, the effect of this drug on the hepatic extraction of insulin is controversial. This investigation uses direct techniques in conscious normal dogs to examine the impact of glyburide therapy (2.5 mg twice daily for 4 weeks) on glucose homeostasis. Preparatory surgery included placement of Doppler flow probes on hepatic vessels and insertion of catheters in carotid artery, portal vein, hepatic vein, and renal vein. After recovery from surgery, animals underwent an intravenous glucose tolerance test ([IGTT] 0.3 g - kg (-1) intravenous glucose bolus) and an insulin infusion clamp test ([IICT] 2 mU - kg (-1) - min (-1) intravenous insulin during 150 minutes) followed by glyburide therapy. After 4 weeks, the IGTT and IICT were repeated. Glyburide increased the insulin secretory response during the late phase of the IGTT and augmented glucose clearance during the IICT. Hepatic extraction of insulin was also stimulated by glyburide. We conclude that the hypoglycemic action of long-term glyburide administration involves stimulation of both insulin secretion by the pancreas and glucose disposal by peripheral tissues. In addition, glyburide augments the extraction of insulin by the liver, and such an effect might prevent the development of sustained high levels of insulin in blood perusing peripheral tissues.

Animals↗

The latency of the cat vestibulo-ocular reflex before and after short- and long-term adaptation.

Latencies of normal and adapted feline vestibulo-ocular reflex (VOR) were studied in five cats by applying +/- 20 degrees/s horizontal head velocity steps (4000 degrees/s2 acceleration) and measuring the elicited horizontal or vertical reflex eye responses. Normal VOR latency was 13.0 ms +/- 1.9 SD. Short-term adaptation was then accomplished by using 2 h of paired horizontal sinusoidal vestibular stimulation and phase-synchronized vertical optokinetic stimulation (cross-axis adaptation). For long-term adaptation, cats wore x 0.25 or x 2.2 magnifying lenses for 4 days. The cats were passively rotated for 2 h/day and allowed to walk freely in the laboratory or their cages for the remainder of the time. The latency of the early (primary) adaptive response was 15.2 ms +/- 5.2 SD for cross-axis adaptation and 12.5 ms +/- 3.9 SD for lens adaptation. This short-latency response appeared within 30 min after beginning the adaptation procedure and diminished in magnitude overnight. A late (secondary) adaptive response with latency of 76.8 ms +/- 7.0 SD for cross-axis adaptation and 68.1 ms +/- 8.8 SD for lens adaptation appeared after approximately 2 h of adaptation. It had a more gradual increase in magnitude than the primary response and did not diminish in magnitude overnight. These data suggest that brainstem VOR pathways are a site of learning for adaptive VOR modification, since the primary latency is short and has a similar latency to that of the normal VOR.

Adaptation, Physiological↗

Milia cysts along the nasal groove in a child.

The occurrence of transverse linear milia cysts over the dorsum of the nose in an 11-year-old girl is described. Two younger sisters of the proband had a conspicuous nasal groove at the same site without milia. The anatomical basis and the pathogenesis of the so-called 'transverse nasal crease' are reviewed.

Child↗

Relationship of IL-2, IL-2R (CD25+), soluble IL-2R and IL-4 with disease activity in SLE patients.

The plasma levels of interleukin-4 (IL-4), interleukin-2 (IL-2), soluble receptor of IL-2 (IL-2R) and T cell expression of IL-2 receptor chain (CD25+) were determined in an attempt to relate these parameters with disease activity in systemic lupus erythematosus (SLE). IL-4, IL-2 and sIL-2R plasma levels of SLE patients were significantly higher than those of the control group (P < 0.05) while CD25+ expression was similar in both groups. Only sIL-2R levels were significantly higher (P < 0.05) in active than in inactive patients.

Adolescent↗

Pathway and carbon sources for hepatic glycogen repletion in dogs.

The present studies were undertaken to quantitate the relative contributions of the indirect and direct pathways for hepatic glycogen repletion and to determine the role of splanchnic tissues in provision of C precursors used for the indirect pathway. For this purpose, we administered oral glucose (1.4 g/kg) enriched with [1-14C]glucose to 18-h fasted dogs and measured net hepatic and net gastrointestinal glucose, lactate, and alanine balance, hepatic and gastrointestinal fractional extraction [( 3H]lactate), release and uptake of lactate, as well as the total amount of hepatic glycogen formed from the oral glucose and the 14C labeling pattern of the glycogen-glucose C. Although net hepatic glucose uptake (8.7 +/- 0.6 g, 27% of the oral load) exceeded the amount of glycogen formed from the oral glucose (6.3 +/- 1.1 g), analysis of radioactivity in C-1 of the glycogen glucose indicated that nearly 50% of the glycogen was formed by the indirect pathway. Net hepatic uptake of lactate (1.4 +/- 0.1 g) and alanine (1.5 +/- 0.1 g) could account for greater than 90% of glycogen formed by the indirect pathway if all of the lactate and alanine taken up by the liver had been incorporated into glycogen. Release of lactate and alanine by splanchnic tissues approximated the amount of lactate and alanine taken up by the liver. However, in addition to taking up lactate, the liver also produced nearly as much lactate as the gastrointestinal tract (1.8 +/- 0.2 vs. 2.0 +/- 0.3 g, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗